When used alongside AstraZeneca’s Imfinzi, the bispecific T cell engager Imdelltra extended survival by eight months versus Imfinzi alone in Phase 3 study testing the combo in a first-line maintenance setting—a potentially “practice-changing” outcome, according to Truist Securities.
New Phase 3 data show that Amgen’s Imdelltra, when combined with AstraZeneca’s Imfinzi, lowered the risk of death and extended survival by eight months when used as a first-line maintenance treatment option in patients with extensive-stage small cell lung cancer.
In the DeLLphi-305 study, Amgen compared Imdelltra plus Imfinzi against Imfinzi alone, enrolling 563 patients with extensive-stage small cell lung cancer (ES-SCLC) who had completed prior treatment with Imfinzi, platinum chemotherapy and the chemotherapeutic agent etoposide and whose cancers had not progressed, according to a Saturday release. Amgen toplined outcomes from DeLLphi-305 last month, though the pharma did not provide data specifics at the time.
Now, the company has presented additional details at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, as well as published the results in The New England Journal of Medicine.
At a median follow-up of 16 months, Imdelltra plus Imfinzi met the study’s primary outcome of overall survival (OS), significantly reducing the risk of death by 58% versus Imfinzi alone. Patients treated with Imdelltra plus Imfinzi lived for a median of 21.1 months, versus 12.7 months for those receiving Imfinzi alone.
Meanwhile, at 13.9 months of median follow-up, the treatment combo lowered the risk of disease progression or death by 66% lower as compared with Imfinzi alone; median progression-free survival was 7.4 months versus 1.9 months, respectively.
These detailed data from Imdelltra and Imfinzi are potentially “practice-changing” in the first-line maintenance ES-SCLC setting, analysts at Truist Securities said in a Sunday afternoon note. Amgen plans to bring DeLLphi-305’s findings to regulatory authorities worldwide “with urgency,” Jay Bradner, executive vice president of R&D, said in a prepared statement.
“For a disease where durable survival has remained extremely difficult to achieve, the magnitude and consistency of benefit in DeLLphi-305 are striking,” Jacob Sands, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in a statement alongside Amgen’s release. “Importantly, the benefit was seen across clinically relevant groups, including patients with brain metastases.”
Analysts across the board were enthusiastic about Amgen’s data. Guggenheim Partners on Sunday wrote that the DeLLphi-305 data “are clearly very impressive,” noting that the combo regimen also delivered consistent benefit across high-risk patient groups.
The firm forecasts around $1 billion in U.S. sales of Imdelltra this year, though the analyst added that expanding into the first-line maintenance setting could be “the largest incremental opportunity of the franchise, as it would extend duration of therapy and move the drug into a setting where more patients are still fit enough to be treated.”
DeLLphi-305 “delivered a clear win in this setting,” Guggenheim continued.
If the pharma secures an expansion, Imdelltra’s addressable population in the U.S. could potentially expand by 1.7 times to around 21.6 thousand patients in the first-line maintenance setting, Truist said. The drug’s total addressable market is around 12,900 patients under its current second-line label.
As for safety, Amgen at ESMO reported that 20.9% of patients treated with the combo regimen experienced treatment-emergent adverse events that were deemed severe or medically significant or worse. The rate of these toxicities was 10.8% in those on Imfinzi alone.
Nearly half of patients on Imdelltra experienced cytokine release syndrome, a temporary systemic inflammatory reaction that typically comes with cell therapies, though most were mild or moderate. Amgen reported no deaths.
Imdelltra is a bispecific T cell engager designed to target the DLL3 and CD3 proteins, in turn triggering the activation of T cells and prompting them to attack cancer cells. The drug was first approved in May 2024 for ES-SCLC, though its current label only allows its use in patients in whom cancer has progressed after platinum-based chemotherapy.
Amgen continues to develop Imdelltra for SCLC—for which antibody-drug conjugates (ADCs) could offer combo opportunities, Truist noted on Sunday.
The firm pointed to the ongoing early-stage DeLLphi-310 study combining Imdelltra with MediLink Therapeutics and Roche’s ADC YL201, with or without Imfinzi, for the treatment of ES-SCLC. There’s also the Phase 1 DeLLphi-313 trial, which is combining Imdelltra with Zai Lab’s ZL-1310, with or without Imfinzi, for patients with SCLC.
“We could see these programs broadening Imdelltra’s role beyond the current chemo-based paradigm” in ES-SCLC, Truist analysts said.
Aside from broadening Imdelltra’s scope in SCLC, Amgen also plans to test Imdelltra in other cancers, including neuroendocrine carcinomas, the pharma revealed in its ESMO presentation. Amgen is considering programs in other DLL3-expressing tumor types, including melanoma, certain gliomas and neuroblastomas in children, according to a Sunday note from Mizuho Securities.
